title: TXNIP maintains the hematopoietic cell pool by switching the function of p53 under oxidative stress.
abstract: Reactive oxygen species (ROS) are critical determinants of the fate of hematopoietic stem cells (HSCs) and hematopoiesis. Thioredoxin-interacting protein (TXNIP), which is induced by oxidative stress, is a known regulator of intracellular ROS. Txnip(-/-) old mice exhibited elevated ROS levels in hematopoietic cells and showed a reduction in hematopoietic cell population. Loss of TXNIP led to a dramatic reduction of mouse survival under oxidative stress. TXNIP directly regulated p53 protein by interfering with p53- mouse double minute 2 (MDM2) interactions and increasing p53 transcriptional activity. Txnip(-/-) mice showed downregulation of the antioxidant genes induced by p53. Introduction of TXNIP or p53 into Txnip(-/-) bone marrow cells rescued the HSC frequency and greatly increased survival in mice following oxidative stress. Overall, these data indicate that TXNIP is a regulator of p53 and plays a pivotal role in the maintenance of the hematopoietic cells by regulating intracellular ROS during oxidative stress.
authors.affiliation: Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon 305-806, Republic of Korea.
authors.forename: Haiyoung
authors.initials: H
authors.lastname: Jung
authors.forename: Mi Jeong
authors.initials: MJ
authors.lastname: Kim
authors.forename: Dong Oh
authors.initials: DO
authors.lastname: Kim
authors.forename: Won Sam
authors.initials: WS
authors.lastname: Kim
authors.forename: Sung-Jin
authors.initials: SJ
authors.lastname: Yoon
authors.forename: Young-Jun
authors.initials: YJ
authors.lastname: Park
authors.forename: Suk Ran
authors.initials: SR
authors.lastname: Yoon
authors.forename: Tae-Don
authors.initials: TD
authors.lastname: Kim
authors.forename: Hyun-Woo
authors.initials: HW
authors.lastname: Suh
authors.forename: Sohyun
authors.initials: S
authors.lastname: Yun
authors.forename: Jeong-Ki
authors.initials: JK
authors.lastname: Min
authors.forename: Hee Gu
authors.initials: HG
authors.lastname: Lee
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Lee
authors.forename: Hee-Jun
authors.initials: HJ
authors.lastname: Na
authors.forename: Dong Chul
authors.initials: DC
authors.lastname: Lee
authors.forename: Hyoung-Chin
authors.initials: HC
authors.lastname: Kim
authors.forename: Inpyo
authors.initials: I
authors.lastname: Choi
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000502:physiology; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D016026:Bone Marrow Transplantation; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D018384:Oxidative Stress / Q000502:physiology*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013879:Thioredoxins / Q000235:genetics / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D000975:Antioxidants; D002352:Carrier Proteins; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; C445672:Txnip protein, mouse; D013879:Thioredoxins; C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2